RESUMEN
Background & Aims: In France, bulevirtide (BLV) became available in September 2019 through an early access program to treat patients with HDV. The aim of this analysis was to evaluate the efficacy and safety of BLV in patients with HIV and HDV coinfection. Methods: Patients received BLV 2 mg ± pegylated interferon-α (pegIFNα) according to the physician's decision. The primary endpoint (per-protocol analysis) was the virological response rate at Week 48, defined as the proportion of patients with undetectable serum HDV RNA or a HDV RNA decline >2 log10 IU/ml from baseline. Results: The characteristics of the 38 patients were as follows: 28 male, mean age 47.7 years, and mean baseline HDV RNA viral load 5.7 ± 1.2 log10 IU/ml. Median HIV viral load and mean CD4 count were 32 (30-65) copies/ml and 566 ± 307/mm3, respectively. Eight patients stopped treatment before Week 48. At Week 48, 10 of 19 patients (52.6%) in the 2 mg BLV group and five of seven patients (71.4%) in the 2 mg BLV + pegIFNÉ group had reached virological response (no HDV RNA available in four patients). At Week 48, seven of 19 patients in the 2 mg BLV group and three of six patients in the 2 mg BLV + pegIFNÉ group had a combined response (virological response and normal alanine aminotransferase level). Conclusions: Adults living with HIV coinfected with HDV can be treated by BLV with a virological response in more than 50% of patients. The combination of BLV and pegIFNÉ showed a strong virological response. Impact and implications: Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug-drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug-drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug-drug interaction is reported.
Asunto(s)
Dióxido de Carbono , Carcinoma Hepatocelular , Insuflación , Neoplasias Hepáticas , Microondas , Neoplasias Peritoneales , Humanos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Microondas/uso terapéutico , Dióxido de Carbono/administración & dosificación , Insuflación/efectos adversos , Masculino , Anciano , Persona de Mediana Edad , Ablación por Radiofrecuencia/efectos adversosRESUMEN
BACKGROUND & AIMS: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC. METHODS: A total of 332 patients with rPBC after LT were evaluated from 28 centers across Europe, North and South America. The median age at the time of rPBC was 58.0 years [IQR 53.2-62.6], and 298 patients (90%) were female. The biochemical response was measured with serum levels of alkaline phosphatase (ALP) and bilirubin, and Paris-2, GLOBE and UK-PBC scores at 1 year after UDCA initiation. RESULTS: During a median follow-up of 8.7 years [IQR 4.3-12.9] after rPBC diagnosis, 52 patients (16%) had graft loss and 103 (31%) died. After 1 year of UDCA initiation the histological stage at rPBC (hazard ratio [HR] 3.97, 95% CI 1.36-11.55, p = 0.01), use of prednisone (HR 3.18, 95% CI 1.04-9.73, p = 0.04), ALP xULN (HR 1.59, 95% CI 1.26-2.01, p <0.001), Paris-2 criteria (HR 4.14, 95% CI 1.57-10.92, p = 0.004), GLOBE score (HR 2.82, 95% CI 1.71-4.66, p <0.001), and the UK-PBC score (HR 1.06, 95% CI 1.03-1.09, p <0.001) were associated with graft survival in the multivariate analysis. Similar results were observed for overall survival. CONCLUSION: Patients with rPBC and disease activity, as indicated by standard PBC risk scores, have impaired outcomes, supporting efforts to treat recurrent disease in similar ways to pre-transplant PBC. IMPACT AND IMPLICATIONS: One in three people who undergo liver transplantation for primary biliary cholangitis develop recurrent disease in their new liver. Patients with recurrent primary biliary cholangitis and incomplete response to ursodeoxycholic acid, according to conventional prognostic scores, have worse clinical outcomes, with higher risk of graft loss and mortality in similar ways to the disease before liver transplantation. Our results supportsupport efforts to treat recurrent disease in similar ways to pre-transplant primary biliary cholangitis.
RESUMEN
BACKGROUND: Partial splenic embolization (PSE) has been proposed to treat the consequences of hypersplenism in the context of portal hypertension, especially thrombocytopenia. However, a high morbidity/mortality rate has made this technique unpopular. We conducted a multicenter retrospective nationwide French study to reevaluate efficacy and tolerance. METHODS: All consecutive patients who underwent PSE for hypersplenism and portal hypertension in 7 tertiary liver centers between 1998 and 2023 were included. RESULTS: The study population consisted of 91 procedures in 90 patients, with a median age of 55.5 years [range 18-83]. The main cause of portal hypertension was cirrhosis (84.6 %). The main indications for PSE were (1) an indication of medical treatment or radiological/surgical procedure in the context a severe thrombocytopenia (59.3 %), (2) a chronic hemorrhagic disorder associated with a severe thrombocytopenia (18.7 %), and (3) a chronic pain associated with a major splenomegaly (9.9 %). PSE was associated with a transjugular intrahepatic portosystemic shunt in 20 cases. Median follow-up after PSE was 41.9 months [0.5-270.5]. Platelet count increased from a median of 48.0 G/L [IQR 37.0; 60.0] to 100.0 G/L [75.0; 148]. Forty-eight patients (52.7 %) had complications after PSE; 25 cases were considered severe (including 7 deaths). A Child-Pugh B-C score (p < 0.02) was significantly associated with all complications, a history of portal vein thrombosis (p < 0.01), and the absence of prophylactic antibiotherapy (p < 0.05) with severe complications. CONCLUSION: Our results strongly confirm that PSE is very effective, for a long time, although a quarter of the patients experienced severe complications. Improved patient selection (exclusion of patients with portal vein thrombosis and decompensated cirrhosis) and systematic prophylactic antibiotherapy could reduce morbidity and early mortality in the future.
Asunto(s)
Embolización Terapéutica , Hiperesplenismo , Hipertensión Portal , Humanos , Estudios Retrospectivos , Embolización Terapéutica/métodos , Persona de Mediana Edad , Anciano , Adulto , Femenino , Masculino , Hipertensión Portal/complicaciones , Hipertensión Portal/terapia , Francia/epidemiología , Anciano de 80 o más Años , Adolescente , Adulto Joven , Hiperesplenismo/terapia , Hiperesplenismo/etiología , Trombocitopenia/etiología , Estudios de Cohortes , Factores de TiempoRESUMEN
BACKGROUND AND AIMS: In patients with noncirrhotic chronic extrahepatic portal vein obstruction (EHPVO), data on the morbimortality of abdominal surgery are scarce. APPROACH AND RESULTS: We retrospectively analyzed the charts of 76 patients (78 interventions) with EHPVO undergoing abdominal surgery within the Vascular Disease Interest Group network. Fourteen percent of the patients had ≥1 major bleeding (unrelated to portal hypertension) and 21% had ≥1 Dindo-Clavien grade ≥3 postoperative complications within 1 month after surgery. Fifteen percent had ≥1 portal hypertension-related complication within 3 months after surgery. Three patients died within 12 months after surgery. An unfavorable outcome (ie, ≥1 abovementioned complication or death) occurred in 37% of the patients and was associated with a history of ascites and with nonwall, noncholecystectomy surgical intervention: 17% of the patients with none of these features had an unfavorable outcome, versus 48% and 100% when one or both features were present, respectively. We then compared 63/76 patients with EHPVO with 126 matched (2:1) control patients without EHPVO but with similar surgical interventions. As compared with control patients, the incidence of major bleeding ( p <0.001) and portal hypertension-related complication ( p <0.001) was significantly higher in patients with EHPVO, but not that of grade ≥3 postoperative complications nor of death. The incidence of unfavorable postoperative outcomes was significantly higher in patients with EHPVO than in those without (33% vs. 18%, p =0.01). CONCLUSIONS: Patients with EHPVO are at high risk of major perioperative or postoperative bleeding and postoperative complications, especially in those with ascites or undergoing surgery other than wall surgery or cholecystectomy.
RESUMEN
BACKGROUND & AIMS: One-third of non-cirrhotic portal vein thrombosis (NCPVT) cases are associated with local factors. The risk of rethrombosis after anticoagulation withdrawal is unknown. We aimed to determine factors associated with new splanchnic or extrasplanchnic thrombotic events in this setting. METHODS: We performed a retrospective study including cases of recent NCPVT associated with local factors. High- and low-risk prothrombotic factors, prespecified according to RIPORT study criteria, were assessed. Univariate and multivariate Cox models assessed the influence of different variables on the occurrence of new thrombotic events. RESULTS: At baseline, 83/154 (53.9%) patients had at least one prothrombotic factor including 50 (32.5%) with a high-risk and 33 (21.4%) with a low-risk prothrombotic factor. Oestrogen-containing contraception was discontinued in all patients. During follow-up, 63/140 (45%) patients had at least one prothrombotic factor, including 47 (33.6%) with a high-risk and 16 (11.4%) with a low-risk prothrombotic factor. Seventeen new thrombotic events occurred after a median follow-up of 52 (IQR 14-62) (min-max 3.0-69.0) months. New thromboses were associated with high-risk factors (hazard ratio [HR] 3.817, 95% CI 1.303-11.180, p = 0.015), but were inversely related to recanalization (HR 0.222, 95% CI 0.078-0.635, p = 0.005) and anticoagulation (HR 0.976, 95% CI 0.956-0.995, p = 0.016). When a high-risk factor was present a new thrombotic event occurred in 7.4%, 14.6%, 14.6% and 28.8% of patients at 1, 3, 5 and 7 years under anticoagulants, respectively, compared to 21.2%, 21.2%, 58% and 58% without anticoagulants, respectively. CONCLUSIONS: In cases of recent NCPVT associated with local factors, high-risk factors for thrombosis are associated with new thrombotic events. Permanent anticoagulation appears beneficial in this high-risk situation. IMPACT AND IMPLICATIONS: In non-cirrhotic portal vein thrombosis (NCPVT) associated with local factors, systematic screening for prothrombotic factors is recommended, but the prevalence of the latter is not clearly established, and the risk of recurrent intra or extrasplanchnic thromboembolism is poorly described. Thus, interest in permanent anticoagulation remains. NCPVT associated with local factors is a matter of concern for hepatologists, gastroenterologists and digestive surgeons. Due to a lack of knowledge, practices are heterogeneous. Our findings highlight that systematic screening for prothrombotic factors in NCPVT is needed even when associated with local factors, as it may justify long-term anticoagulation for the prevention of new intra or extrasplanchnic thrombotic events in at least one-third of cases. The interest in long-term anticoagulation should be investigated prospectively in the absence of high-risk prothrombotic factors. CLINICAL TRIAL NUMBER: NCT0536064.
RESUMEN
BACKGROUND & AIMS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy (DS) was adopted in France in 2015 in patients listed for any single HCC treated with resection or thermal ablation during the waiting phase. The DS involves postponing LT until recurrence. The purpose of this study was to evaluate the DS to make sure that it did not hamper pre- and post-LT outcomes. METHODS: Patients listed for HCC in France between 2015 and 2018 were studied. After data extraction from the national LT database, 2,025 patients were identified and classified according to six groups: single tumor entering DS, single tumor not entering DS, multiple tumors, no curative treatment, untreatable HCC or T1 tumors. Kaplan-Meier estimates of the 18-month risk of dropout for death, too sick to be transplanted or tumor progression before LT, 5-year post-LT HCC recurrence and post-LT survival rates were compared. RESULTS: Median waiting-time in the DS group was 910 days. Pre-LT dropout probability was significantly lower in the DS group compared to other groups (13% vs. 19%, p = 0.0043) and significantly higher in the T1 group (25.4%, p = 0.05). Post-LT HCC recurrence rate in the multiple nodules group was significantly higher (19.6%, p = 0.019), while 5-year post-LT survival did not differ among groups and was 74% in the DS group (p = 0.22). CONCLUSION: The DELTA-HCC study shows that DS does not negatively impact either pre- nor post-LT patient outcomes, and has the potential to allow for redistribution of organs to patients in more urgent need of LT. It can reasonably be proposed and pursued. The unexpectedly high risk of dropout in T1 patients seems related to the MELD-based offering rules underserving this subgroup. IMPACTS AND IMPLICATIONS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy was adopted in France in 2015. It involves postponing LT until recurrence in patients listed for any single HCC curatively treated by surgical resection or thermal ablation. The DELTA-HCC study was conducted to evaluate this nationwide strategy. It shows in a European LT program that delayed strategy does not negatively impact pre- nor post-LT patient outcomes and is relevant to up to 20% of LT candidates; thus, it could potentially enable the redistribution of organs to patients in more urgent need of LT. Such a delayed strategy can reasonably be pursued and extended to other LT programs. Of note, an unexpectedly high risk of dropout in T1 patients, seemingly related to MELD-based offering rules which underserve these patients, calls for further scrutinization and revision of allocation rules in this subgroup.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Listas de Espera , Humanos , Trasplante de Hígado/métodos , Trasplante de Hígado/estadística & datos numéricos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Francia/epidemiología , Anciano , Listas de Espera/mortalidad , Recurrencia Local de Neoplasia/epidemiología , Tasa de Supervivencia , Tiempo de Tratamiento/estadística & datos numéricos , Factores de Tiempo , Estudios RetrospectivosRESUMEN
BACKGROUND: In recent years, age at liver transplantation (LT) has markedly increased. In the context of organ shortage, we investigated the impact of recipient age on post-transplantation mortality. METHODS: All adult patients who received a first LT between 2007 and 2017 were included in this cross-sectional study. Recipients' characteristics at the time of listing, donor and surgery data, post-operative complications and follow-up of vital status were retrieved from the national transplantation database. The impact of age on 5-year overall mortality post-LT was estimated using a flexible multivariable parametric model which was also used to estimate the association between age and 10-year net survival, accounting for expected age- and sex-related mortality. RESULTS: Among the 7610 patients, 21.4% were aged 60-65 years, and 15.7% over 65. With increasing age, comorbidities increased but severity of liver disease decreased. Older recipient age was associated with decreased observed survival at 5 years after LT (p < .001), with a significant effect particularly during the first 2 years. The linear increase in the risk of death associated with age does not allow any definition of an age's threshold for LT (p = .832). Other covariates associated with an increased risk of 5-year death were dialysis and mechanical ventilation at transplant, transfusion during LT, hepatocellular carcinoma and donor age. Ten-year flexible net survival analysis confirmed these results. CONCLUSION: Although there was a selection process for older recipients, increasing age at LT was associated with an increased risk of death, particularly in the first years after LT.
Asunto(s)
Trasplante de Hígado , Humanos , Trasplante de Hígado/mortalidad , Persona de Mediana Edad , Masculino , Femenino , Francia/epidemiología , Anciano , Factores de Edad , Estudios Transversales , Adulto , Factores de Riesgo , Complicaciones Posoperatorias/mortalidad , Análisis de Supervivencia , Enfermedad Hepática en Estado Terminal/cirugía , Enfermedad Hepática en Estado Terminal/mortalidad , Receptores de Trasplantes/estadística & datos numéricosRESUMEN
BACKGROUND: After organ transplantation, strategies for simplifying the therapeutic regimen may improve adherence and prevent acute organ rejection and/or late graft loss. The present study aimed to evaluate the safety and efficacy of conversion from everolimus (EVR) twice daily to sirolimus (SIR) once daily in a large cohort of liver transplantation (LT) patients. METHODS: We included 108 LT patients with at least 12 months of post-transplant follow-up and no rejection episodes in the last year. Conversion was based on a 1:1 ratio (but eventually adapted to available formulations of SIR). RESULTS: The median age at the time of conversion was 68.9 years (range: 26.1-83.6); 75.0% were men. The main indications for mTOR inhibitor use were renal failure (38.9%) and/or a history of malignancy (37.0%). Median conversion time after LT was 14.8 years (range: 2.3-31.5). The median dose of EVR and SIR (initially) was 1.50 mg/day (range: 0.5-4.5). The mean follow-up after conversion was 15.8±4.4 months. Median serum EVR/SIR trough levels before/after conversion were 3.85 ng/mL vs. 6.32 ng/mL (p < 0.05), i.e. a 1:1.64 ratio. At the end of follow-up after conversion, the median dose of SIR was 1.25 mg/day (range: 0.5-3.5), and the mean serum SIR trough level was 5.23 ng/mL; 9 patients (8.3%) had returned to EVR, because of side effects (mainly digestive), that resolved thereafter. No biopsy-proven acute rejection episode was observed. Finally, 87.1% of patients considered the conversion beneficial and the cost was reduced by 50.3%. CONCLUSION: The results of our study indicate that conversion from once-daily EVR to once-daily SIR in stable LT patients is safe, but needs dose adaptations and careful monitoring.
Asunto(s)
Trasplante de Hígado , Trasplante de Órganos , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Everolimus , Sirolimus , Inmunosupresores/uso terapéutico , Trasplante de Hígado/efectos adversos , Rechazo de Injerto/prevención & control , Tacrolimus/efectos adversos , Receptores de TrasplantesRESUMEN
BACKGROUND: Liver transplant recipients are at risk of tuberculosis, which is particularly difficult-to diagnose and to treat in this population. METHODS: Retrospective study of all cases of tuberculosis diagnosed from 2007 to 2022 in the French network of liver transplant sites. RESULTS: Twenty-three liver transplant recipients were diagnosed with tuberculosis (six females, median age 59 years [interquartile range, 54-62]), with a median time lapse of 10 months [5-40.5] after transplant, and 38 days [26-60] after symptoms onset. Primary modes of pathogenesis were latent tuberculosis reactivation (n = 15) and transplant-related transmission (n = 3). Even though most patients with pre-transplant data had risk factors for tuberculosis (11/20), IFN-gamma release assay was performed in only three. Most cases involved extra-pulmonary tuberculosis (20/23, 87 %). With median follow-up of 63 months [24-108], five patients died (22 %), including four tuberculosis-related deaths. CONCLUSIONS: Extrapulmonary tuberculosis is a severe disease in liver transplant recipients. Systematic pre-transplant screening of latent tuberculosis may prevent most of them.
Asunto(s)
Tuberculosis Latente , Trasplante de Hígado , Tuberculosis , Femenino , Humanos , Persona de Mediana Edad , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/epidemiología , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Factores de RiesgoRESUMEN
[This corrects the article DOI: 10.3389/fimmu.2023.1326078.].
Asunto(s)
Carcinoma Hepatocelular , Heterocigoto , Lipasa , Cirrosis Hepática , Neoplasias Hepáticas , Proteínas de la Membrana , Mutación , Humanos , Proteínas de la Membrana/genética , Carcinoma Hepatocelular/genética , Lipasa/genética , Cirrosis Hepática/genética , Neoplasias Hepáticas/genética , Hígado Graso/genética , Masculino , Femenino , Apolipoproteína B-100/genética , Persona de Mediana Edad , Aciltransferasas , Fosfolipasas A2 Calcio-IndependienteRESUMEN
Autoimmune hepatitis (AIH) may recur after liver transplantation (LT). The aims of this study were to evaluate the incidence and risk factors for recurrent autoimmune hepatitis (rAIH). A multicenter retrospective French nationwide study, including all patients aged ≥16 transplanted for AIH, with at least 1 liver biopsy 1 year after LT, was conducted between 1985 and 2018. Risk factors for rAIH were identified using a multivariate Cox regression model. Three hundred and forty-four patients were included (78.8% women) with a median age at LT of 43.6 years. Seventy-six patients (22.1%) developed recurrence in a median time of 53.6 months (IQR, 14.1-93.2). Actuarial risk for developing rAIH was 41.3% 20 years after LT. In multivariate analysis, the strongest risk factor for rAIH was cytomegalovirus D+/R- mismatch status (HR=2.0; 95% CI: 1.1-3.6; p =0.03), followed by associated autoimmune condition. Twenty-one patients (27.6% of rAIH patients) developed liver graft cirrhosis after rAIH. Independent risk factors for these severe forms of rAIH were young age at LT, IgG levels >20.7 g/L, and LT in the context of (sub)fulminant hepatitis. Immunosuppression, especially long-term maintenance of corticosteroid therapy, was not significantly associated with rAIH. Recurrence of AIH after LT is frequent and may lead to graft loss. Recurrence is more frequent in young patients with active disease at the time of LT, yet systematic corticosteroid therapy does not prevent it.
Asunto(s)
Hepatitis Autoinmune , Trasplante de Hígado , Humanos , Femenino , Adulto , Masculino , Trasplante de Hígado/efectos adversos , Hepatitis Autoinmune/epidemiología , Hepatitis Autoinmune/cirugía , Inmunosupresores/efectos adversos , Estudios Retrospectivos , Cirrosis Hepática/complicaciones , Corticoesteroides , RecurrenciaRESUMEN
BACKGROUND & AIMS: If alcohol-related liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are now the two main indications for liver transplantation (LT), it has been recognized that both conditions can coexist in varying degrees and the concept of dual-aetiology fatty liver disease (DAFLD) has been proposed. This retrospective study aimed to evaluate, in a cohort of patients transplanted for ALD and NAFLD, the prevalence of DAFLD before LT and the impact on liver graft outcome. METHODS: From 1990 to 2010, all patients who underwent LT for the so-called ALD or NAFLD in our centre were included. Before LT, DAFLD was defined as patients with a history of excessive alcohol consumption and obesity associated with either diabetes or hypertension. Before LT, patients were separated into three groups: DAFLD, ALD, and NAFLD. Fatty liver graft disease was classified according to the FLIP algorithm. RESULTS: Out of 907, adult LT recipients were identified: 33 DAFLD patients, 333 ALD patients, and 24 NAFLD patients. After LT, ALD patients experienced significantly more alcohol relapse than DAFLD patients, who had twice more post-LT metabolic syndrome. Out of 926, post-LT biopsies, DAFLD patients had significantly more fatty liver graft disease due to metabolic syndrome features than ALD patients. CONCLUSION: Our results support that DAFLD recently emerged as an indication of LT. In the future, this particular population needs to be identified as a specific entity since post-LT outcome on the graft is different from ALD and more similar to NAFLD patients.
Asunto(s)
Hepatopatías Alcohólicas , Trasplante de Hígado , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Adulto , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/cirugía , Hepatopatías Alcohólicas/complicaciones , Hepatopatías Alcohólicas/epidemiología , Hepatopatías Alcohólicas/cirugía , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Estudios Retrospectivos , RecurrenciaRESUMEN
BACKGROUND: Diffusion-weighted imaging (DWI) has been considered for chronic liver disease (CLD) characterization. Grading of liver fibrosis is important for disease management. PURPOSE: To investigate the relationship between DWI's parameters and CLD-related features (particularly regarding fibrosis assessment). STUDY TYPE: Retrospective. SUBJECTS: Eighty-five patients with CLD (age: 47.9 ± 15.5, 42.4% females). FIELD STRENGTH/SEQUENCE: 3-T, spin echo-echo planar imaging (SE-EPI) with 12 b-values (0-800 s/mm2 ). ASSESSMENT: Several models statistical models, stretched exponential model, and intravoxel incoherent motion were simulated. The corresponding parameters (Ds , σ, DDC, α, f, D, D*) were estimated on simulation and in vivo data using the nonlinear least squares (NLS), segmented NLS, and Bayesian methods. The fitting accuracy was analyzed on simulated Rician noised DWI. In vivo, the parameters were averaged from five central slices entire liver to compare correlations with histological features (inflammation, fibrosis, and steatosis). Then, the differences between mild (F0-F2) or severe (F3-F6) groups were compared respecting to statistics and classification. A total of 75.3% of patients used to build various classifiers (stratified split strategy and 10-folders cross-validation) and the remaining for testing. STATISTICAL TESTS: Mean squared error, mean average percentage error, spearman correlation, Mann-Whitney U-test, receiver operating characteristic (ROC) curve, area under ROC curve (AUC), sensitivity, specificity, accuracy, precision. A P-value <0.05 was considered statistically significant. RESULTS: In simulation, the Bayesian method provided the most accurate parameters. In vivo, the highest negative significant correlation (Ds , steatosis: r = -0.46, D*, fibrosis: r = -0.24) and significant differences (Ds , σ, D*, f) were observed for Bayesian fitted parameters. Fibrosis classification was performed with an AUC of 0.92 (0.91 sensitivity and 0.70 specificity) with the aforementioned diffusion parameters based on the decision tree method. DATA CONCLUSION: These results indicate that Bayesian fitted parameters may provide a noninvasive evaluation of fibrosis with decision tree. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.
Asunto(s)
Hígado Graso , Hepatopatías , Femenino , Humanos , Masculino , Estudios Retrospectivos , Teorema de Bayes , Cirrosis Hepática/patología , Imagen de Difusión por Resonancia Magnética/métodos , Movimiento (Física)RESUMEN
BACKGROUND AND AIM: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver diseases. APPROACH AND RESULTS: Retrospective multicenter analysis of liver disease (transaminases > 30 IU/L and/or abnormal liver imaging) in patients with TRG mutations. Main measurements were characteristics, outcomes, and risk factors of liver disease in a TRG mutations cohort. The prevalence of liver disease was compared to a community-based control group (n = 1190) stratified for age and matched 1:3 for known risk factors of liver disease. Among 132 patients with TRG mutations, 95 (72%) had liver disease, with associated lung, blood, skin, rheumatological, and ophthalmological TRG diseases in 82%, 77%, 55%, 39%, and 30% of cases, respectively. Liver biopsy was performed in 52/95 patients, identifying porto-sinusoidal vascular disease in 48% and advanced fibrosis/cirrhosis in 15%. After a follow-up of 21 months (12-54), ascites, hepato-pulmonary syndrome, variceal bleeding, and HCC occurred in 14%, 13%, 13%, and 2% of cases, respectively. Five-year liver transplantation-free survival was 69%. A FIB-4 score ≥ 3·25 and ≥1 risk factor for cirrhosis were associated with poor liver transplantation-free survival. Liver disease was more frequent in patients with TRG mutations than in the paired control group [80/396, (20%)], OR 12.9 (CI 95%: 7.8-21.3, p < 0.001). CONCLUSIONS: TRG mutations significantly increase the risk of developing liver disease. Although symptoms may be mild, they may be associated with severe disease. Porto-sinusoidal vascular disease and cirrhosis were the most frequent lesions, suggesting that the mechanism of action is multifactorial.
RESUMEN
The clinical features and short-term prognosis of patients admitted to the intensive care unit for herpes hepatitis are lacking. Of 33 patients admitted between 2006 and 2022, 22 were immunocompromised, 4 were pregnant women, and 23 died. Sixteen patients developed a hemophagocytic syndrome. Acyclovir was initiated a median (interquartile range) of 1 (0-3) day after admission.